PK‐PD modeling of buprenorphine in cats: intravenous and oral transmucosal administration¹

Abstract

The pharmacokinetics and thermal antinociceptive effects of buprenorphine after intravenous (i.v.) or oral transmucosal (OTM) administration were studied in six adult cats. Plasma buprenorphine concentrations were measured using radioimmunoassay in a crossover study after a dose of 20 microg/kg given by the i.v. or OTM route. Oral pH was measured. Blood for drug analyses was collected before, and at 1, 2, 4, 6, 10, 15, 30, and 60 min and at 2, 4, 6, 8, 12, and 24 h after treatment. Thermal thresholds were measured before treatment, then following treatment every 30 min to 6 h, every 1 hour to 12 h and at 24 hours postadministration. Plasma buprenorphine concentration effect relationships were analyzed using a log-linear effect model. Oral pH was 9 in each cat. Peak plasma buprenorphine concentration was lower and occurred later in the OTM group but median bioavailability was 116.3%. Thermal thresholds increased significantly between 30 and 360 min in both groups. Peak effect was at 90 min and there was no difference at any time between the two groups. There was distinct hysteresis between plasma drug concentration and effect in both groups. Overall, OTM administration of buprenorphine is as effective as i.v. treatment and offers a simple, noninvasive method of administration which produces thermal antinociception for up to 6 h in cats.

2015 AAHA/AAFP Pain Management Guidelines for Dogs and Cats

“…15 The oral transmucosal or buccal route of administration for buprenorphine may have clinical efficacy as well. 16,17 < The individual effect of any opioid, including duration, may vary widely from…”

Pharmacokinetic and Pharmacodynamic Assessments of Tapentadol in Yellow-Bellied Slider Turtles (Trachemys Scripta Scripta) after a Single Intramuscular Injection

“…); this varies from an earlier study reporting PK/PD of buprenorphine in cats. 36 The linear relationship between TAP plasma concentration and effect might be accounted for by the rapid blood-brain equilibration and its high MOR affinity. 37 This is consistent with the high lipophilicity of TAP.…”

Veterinary Anesthesia

“…The fentanyl patch is also commonly used in many species, with relatively predictable uptake and efficacy. Buprenorphine can be administered transmucosally to cats, due to the alkaline pH of cat saliva and a pKa of buprenorphine of 8.24 [34,35]. Unlike humans, most formulations of opioids that are marketed for oral administration are not useful in veterinary species, due to significant first-pass metabolism; for example, oral administration of MS Contin to dogs results in negligible serum concentrations [36].…”